PROJECT SUMMARY B cell responses to particulate antigens Two biophysical attributes shared by most animal viruses are the display of viral-specific proteins at certain densities on the surface of individual virions and the encapsulation of viral genome inside the virion. A threshold density of viral surface proteins is important to ensure efficient viral infection of host cells. From the perspective of the host, a threshold density of viral surface proteins may also be critical for the recognition by germline B cells for efficient mounting of humoral responses. The encapsulated genetic material may also stimulate B cells through the Toll-like receptors. Substantial mechanistic studies at the single-molecule level and imaging of live cells have revealed the sensitivity of B cells to the density of antigens. However, at the mechanistic level, it remains largely uncharacterized how B cells may recognize and respond to the collective attributes of a virus, including the spatial density of proteins and the internal nucleic acids. This project aims to test both functional and mechanistic relevance of viral features on B cell responses by developing quantitative assays both in vivo and in vitro. The success of this project will yield important mechanistic insights on how B cells may recognize particulate antigens similar in size to viruses and vaccines, and what are the possible functional outcomes of B cells in response to the recognition of these antigens.